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204 Cards in this Set
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What is the difference among:
Macrocytic Anemia Normocytic normochromic Anemia Microcytic hypochromic Anemia |
What is the difference among:
Macrocytic Anemia- defective nuclear maturation; decrease production Normocytic normochromic Anemia- Acute blood loss, hemolytic, renal failure, chronic disease Microcytic hypochromic Anemia- Iron Deficiency |
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Name symptoms of Iron-Deficiency Anemia
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Fatigue
SOB Tachycardia Koilonychia (spoon nails) decreased cognitive function Pica (craving to chew on ice, chalk, crayon or even dirt) |
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Name the glycoprotein that Iron is transfered by
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Transferrin
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What is the normal absorption of Iron?
What is the max? |
Normal: 1-1.4 mg/day
Max: 3-4 mg/day If you are iron deficient you are able to absorb more iron to compensate |
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What is the Iron requirement for:
Infant Child Adult male Adult female Pregnancy |
What is the Iron requirement for:
Infant- 67 ug/kg Child- 22 ug/kg Adult male-13ug/kg Adult female- 21 ug/kg Pregnancy- 80 ug/kg |
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Foods High in Iron?
Foods Low in Iron? |
High:
Meat Brewer's Yeast Wheat germ Egg yolks Oyster Dried beans and fruit Low: Milk Nongreen vegetables |
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Heme Iron vs. Inorganic Iron
which is more available? which is more important? |
Heme iron- more available
Inorganic iron- more important |
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Name 2 Facilitators of Iron Absorption
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1. Ascorbic Acid (Vitamin C)
2. Meats (stimultes gastric acid) |
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Tolerable doses of oral iron in people with iron-deficiency anemia, will deliver at most how much iron/day to the erythroid marrow?
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40-60 mg/day
increases RBC production by 2-3 times |
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Which is absorbed better?
Ferrous or Ferric Salts Name some of theses |
Ferrous are absorbed 3x better
Gluconate Sulfate Fumarate Succinate |
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Name Ferrous Salts from highest percentage of Fe to least
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FEOSTAT= 33% (sulfate)
FEOSOL= 20% (fumarate) FERGON= 12% (gluconate) NIFEREX= (succinate) |
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Name Absorption enhancers for Fe
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increases absorption:
Ascorbic Acid (Vitamin C) Carbohydrates Amino Acids (meat) inorganic salts |
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What are the RDA of iron for:
Pregnant females lactating females males females >50 females 19-50 adolescent males >14 |
What are the RDA of iron for:
Pregnant females= 15mg, then 27 mg lactating females= 9-10 mg males= 8 mg females >50= 8 mg females 19-50= 18 mg adolescent males >14= 11 mg |
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Oral Iron Doses for Iron Deficiency
Adults and Adolescents Neonates, Infants, Children Pregnant Women |
Oral Iron Doses for Iron Deficiency
Adults and Adolescents- 200 mg/day Neonates, Infants, Children- 3 mg/kg/ day Pregnant Women- 15-30 mg/day |
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Oral Side Effects of Iron
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Heartburn
Nausea Upper gastric discomfort Constipation and Diarrhea |
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What is Hemochromatosis?
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Iron overload due to long-continued treatment (Iron Toxicity)
1-2 g in children (12-24months) can lead to death Symptoms: abdominal pain, diarrhea, vomiting, cyanosis, lassitude, drowsiness, hyperventilation |
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Under what conditions do you consider Parenteral Iron?
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Iron Malabsorption
Severe oral iron intolerance Patients with renal disease who are receiving erythropoietin |
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What causes Megablastic Anemia?
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deficiency in:
1. Vitamine B12 2. Folic Acid results in defective synthesis of DNA |
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Name sources for Vitamin B12
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Animal
Bacteria |
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How is Vitamin B12 absorbed?
What test is performed to evaluate the absorption of B12? Is it okay to inject Cyanocobalamin I.V.? |
from the ileum
complex of Intrinsic Factor B12 Intrinsic factor produced by parietal cells (this is why PPI are contraindicated) Schilling test NO- IM or SC only |
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Name some Therapeutic Uses of Vitamin B12
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Trigeminal Neuralgia
Multiple Sclerosis Neuropathies Psychiatric disorders |
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What is the recommended daily requirement for Folic Acid?
What if pregnant or lactating? |
400 ug
500-600 ug |
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What are some drugs that can cause Folate Deficiency?
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anticonvulsants
methotrexate trimethoprim oral contraceptives alcohol |
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A deficiency in what may cause spina bifida, encephaloceles, and anencephaly?
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Folate Deficiency
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Treatment for Folate Deficiency
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Folic Acid (FOLVITE)
Folinic Acid (Leucovorin calcium, citrovorum factor) |
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Side Effects of high Folic Acid?
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decreases antiepileptic actions of:
phenobarbital phenytoin primidone |
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What is the maximum level for Hemoglobin?
What are some Erythropoiesis Stimulating Agents (ESA) |
Max: 12 g/L
Epoetin alfa Darbepoetin alfa (Aranesp) |
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What diseases cause an increase in atherogenic risk?
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coronary heart disease
Ischemic cerebrovascular disease Peripheral vascular disease |
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Saturated fat should not take up more than what percent of total fat intake?
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15%
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What type of fatty acids increase levels of LDL cholesterol?
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Trans fatty acids and saturated fatty acids
NOT unsaturated cis (olive oil) |
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Name the apoliproteins on these lipoproteins:
Chylomicrons VLDL LDL HDL |
Name the apoliproteins on these lipoproteins:
Chylomicrons- A, B48, C (i,ii, iii), E VLDL- B100, C (i,ii,iii), E LDL- B100 HDL- A, C (i,ii,iii), D, E |
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What is the precursor for LDL?
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IDL
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Which Lipoproteins do these functions?
Reverse cholesterol transport Transport of endogenous triglycerides Transport of dietary trigycerides Major cholesterol transport lipoprotein |
Which Lipoproteins do these functions?
HDL- Reverse cholesterol transport VLDL- Transport of endogenous triglycerides Chylomicron- Transport of dietary trigycerides LDL- Major cholesterol transport lipoprotein |
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Lipoprotein Phenotype:
Type I Type IIa Type IIb Type III Type IV Type V |
Lipoprotein Phenotype:
Type I- deficiency in LPL Type IIa- deficiency of LDL receptors Type IIb- High Apo B & defective Apo E Type III- abnormal IDL metabolism Type IV- abnormal VLDL metabolism Type V- abnormal VLDL and chylomicron metabolsim |
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Fiber
vs Bile Acid Sequestrants |
Fiber- decreases cholesterol absorption
Bile Acid Sequestrants- decrease bile acid reabsorption |
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What is the enterohepatic circulation?
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cycle of secretion adn reabsorption of bile salts and cholesterol
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stored in the gall bladder, amphipathic, and acts as detergent to break up dietary lipids
transfered back to liver bound to albumin |
Bile Salts
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Reduces cholesterol adsorbtion in to the blood stream
binds bile salts and cholesterol and prevent its reabsorption |
Sitostanol ester
Fiber |
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group of medication used for binding bile in the gastrointestinal tract; treats hypercholesterolemia and chronic diarrhea
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Bile Acid Sequestrants: Resins
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What is the mechanism of action for bile acid sequestrant?
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Anion-exhange resins (binds anions)
increases bile acid synthesis stimulates production of LDL receptors lowers LDL-C levles increases LDL clearance increase in TG production |
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Name 3 Bile Acid Sequestrants
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1. Cholestyramin (Questran)
2. Colestipol (colestid) 3. Colesevelam (WelChol) Cholestyram and Colestipol are more effective at lowering LDL, while Colesevelam is more effective at raising HDL; both may increase TG |
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Drug interactions with colestipol and cholestyramine?
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binds to other negatively charged drugs
must give other drugs 1 hour before or 4-6 hours after interfere with the absorption of folic acid and fat-soluble vitamines |
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What are some of the uses of Bile Acid Sequestrants?
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1. Adjunct to treatment of hypercholesterolemia
2. Pruritus due to high bile acids; diarrhea associated with excess fecal bile acids 3. Binding toxicologic agents 4. Oxaluria- excess calcium oxalae in the urine |
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Which drugs do Bile Acid Sequestrants interact with?
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Some thiazides
Furosemide Propranolol L-thyroxine Cardiac glycosides Coumadin anticoagulants Some statins |
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Statins Mechanism of Action
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inhibition of HMG-CoA reductase
increase LDL receptors in liver increase LDL clearance |
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What are the LDL levels for:
Optimal Near optimal Borderline High High Very High |
What are the LDL levels for:
Optimal- <100 mg/dl Near optimal 100-129 Borderline High 130-159 High 160-180 Very High >190 |
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Total Cholesterol Levels
Desirable Borderline High High |
Total Cholesterol Levels
Desirable <200 mg/dl Borderline High 200-239 mg/dl High >240 mg/dl |
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HDL Cholesterol Levels
Low High |
HDL Cholesterol Levels
Low < 40 mg/dl (bad) High >60 mg/dl (good) |
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Name the Equivalent Diseases to Coronary Heart Disease
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CHD
Carotid Artery Disease Peripheral Artery Disease Abdominal Aortic Aneurysm |
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Name 5 Risk Factors for Hypercholesteremia
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1. Cigarette Smoking
2. Hypertension (>140/90) 3. Low HDL (<40 mg/dl) 4. Family History of CHD 5. Age: Men 45 Women 55 |
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What are the LDL-Goal and levels at which to consider drug therapy for:
CHD or CHD equivalent >2 risk factors (10-20%) >2 risk factors (<10%) <2 risk factors |
What are the LDL-Goal and levels at which to consider drug therapy for:
CHD or CHD equivalent: <100/ >130 >2 risk factors (10-20%): <130/ >130 >2 risk factors (<10%): <130/ >160 <2 risk factors: <160/ >190 |
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Name of Calculator for estimating 10-year CHD Risk
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Framingham
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Name the 6 Statins with their strengths that are dose equivalent (most potent to least)
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Rosuvastatin 5mg
Atorvastatin 10 mg Simvastatin 20mg Lovastatin 40 mg Pravastatin 40 mg Fluvastatin 80mg |
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When is someone considered to have Metabolic Syndrome?
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when > or = 3 risk factors are present
Waist: male= >40in female= >35 TG: >150 mg/dl HDL: men= <40 women= <50 Blood pressure: >130/85 Fasting glucose: >110 mg/dl |
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Triglyceride levels for:
Normal Borderline High High Very High |
Triglyceride levels for:
Normal <200 Borderline High 200-399 High 400-1000 Very High >1000 |
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Compare LDL cholesterol and Non-HDL Cholesterol goals for:
CHD equivalent >2 Risk Factors 0-1 Risk Factor |
Compare LDL cholesterol and Non-HDL Cholesterol goals for:
LDL-goal/ Non-HDL goal CHD equivalent: <100/ <130 >2 Risk Factors: <130/ <160 0-1 Risk Factor: <160/ <190 |
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No atherosclerosis progress when LDL is below what?
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<67 mg/dl
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Is Diabetes a CHD equivalent?
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YES
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What is the most significant side effect of Statins?
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Myopathy and Rhabdomyolysis
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Doubling the dose of statins will increase the effect by how much?
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~5-6%
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Steps of Plaque formation?
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1. LDL enters artery wall
2. Modified LDL stimulates expression of MCP-1 in endothelial cells 3. Monocytes differentiate into Macrophages 4. Modified LDL indudes Macrophages to release cytokines that stimulate Adhesion molecule expression in endothelial cells 5. Macrophages express receptors that take up modified LDL 6. Macrophages and Foam cells express Growth Factors and Proteinases 7. remnants of VLDL and Chylomicrons are also proinflammatory |
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Where is HDL produced?
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Liver and Intestine
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What is involved in the HDL metabolism and reverse cholesterol transport?
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Nascent HDL picks up FC from macrophage using ABC1
Nascent HDL changes to mature HDL using LCAT Mature HDL with CE now binds SR-BI on Liver |
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HMG-CoA Reductase Inhibitors
(Differences in effect on LDL/ HDL/ TG) Rosuvastatin Atorvastatin Simvastatin Lovastatin Pravastatin Fluvastatin |
HMG-CoA Reductase Inhibitors
(Differences in effect on LDL/ HDL/ TG) Rosuvastatin +++/+++/++ Atorvastatin ++/+/+ Simvastatin ++/++/+++ Lovastatin ++/++/++ Pravastatin +/+/+ Fluvastatin +/+/+ |
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Statin Combos:
Statin-bile acid Statin-Niacin Statin-Fibrate |
Statin Combos:
Statin-bile acid- 20-30% more reduction in LDL-C Statin-Niacin- increases risk of myopathy Statin-Fibrate- useful in patients with both high TG and LDL-C Triple Therapy= up to 70% reduction in LDL-C |
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Four mechanisms by which Statins are thought to prevent cardiovascular diease
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1. Improve endothelial function
2. Modulate inflammatory responses 3. Maintain plaque stability 4. Prevent Thrombus formation |
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What is Myopathy?
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major adverse effect of statins
skeletal inhibition of skeletal muscle sterol synthesis |
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Drug interactions with Statins?
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Macrolides
antifungals cyclosporine phenylpiperazine antidepressants nefazodone pretease inhibitors amiodaron warfarin Both use CYP3A4 |
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Which statins are water soluble and which are lipophilic?
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Lipophilic:
Atorvastatin Simvastatin Lovastatin Fluvastatin Water soluble: Rosuvastatin Pravastatin |
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Statins the use CYP2C9 and can interact with:
Amiodarone Gemfibrozil Fluconazol metronidazole Fluoxetine Warfarin |
Fluvastatin
and Rosuvastatin |
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Which Statin is associated with an increased risk of muscle injury?
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Simvastatin 80mg
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Can Statins be used in Pregnancy?
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NO
Risk Factor X |
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Foods and/or products to avoid when taking statins?
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Ethanol (+)
Grapefruit juice (+) St John's wort (-) |
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How do Fibrates work?
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Fibrates activate PPARs causing transcription of a number of genes on the DNA that facilitate lipid metabolism
They are Amphipathic carboxylic acids |
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What types of elevated TG do Fribrates treat?
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Type III- IDL
Type IV- high VLDL Type V- high VLDL and chylomicron |
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Name 2 Fibrates
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1. Gemfibrozil (Lopid)
2. Fenofibrate (Antara, Lofibra, TriCor, Triglide) |
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What is the active metabolite of Fenofibrate?
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Fenofibrate is a prodrug
active metabolite- fenofibric acid |
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Side Effects of Fibrates
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Stomach upset
Myopathy Rhabdomylysis Lithiasis (predisposition to the formation of gallstones) |
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Drug Interactions with Fibrates
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Warfarin
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What is the importance of Niacin? and what are other names for Niacin?
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Nicotinic acid and Vitamine B3
water soluble vitamin that playes role in energy metabolism deficiency in Niacin leads to Pellagra and Depression |
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Tryptophan is used to synthesize Niacin and Serotonin
therefore, niacin deficiency can cause what? |
Depression b/c lack of serotonin
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What are the actions of Niacin
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Inhibits VLDL secretion
Inhibits free fatty acid release Increases LPL activity Decreases TG synthesis and lipolysis Reduces TG |
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Side Effects of Niacin?
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1. Liver Toxicity
2. Flushing take Aspirin 30 min prior to help prevent flushing the flushing is harmless also could try suspended release instead of immediate release |
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Name 2 Dietary and Biliary Cholesterol Absorption Inhibitors (blocks intestinal absorption of cholesterol)
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1. Ezetimibe (Zetia) 19% decrease in LDL-C
2. Vytorin (simvastatin with acetamide) 52% decrease in LDL-C |
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Name 3 combination drugs for hypercholesteremia
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1. Advicor (Niacin and Lovastatin)- take at bedtime; lowers LDL, TG, VLDL, and blocks cholesterol synthesis
2. Simcor (Niacin ER and Simvastatin) 3. Caduet (Atorvastatin and Amlodipine) blocks cholesterol synthesis and lowers blood pressure |
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Name potential Triglyceride-Lowering Mechanisms of Omega-3 Fatty Acids
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1. Decrease in lipogenesis
2. Increase in Beta-oxidation, phospholipid synthesis, and apo B degradation 3. reduced secretion of VLDL and TG |
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What is in Lovaza?
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DHA
EPA Omega-3 |
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What is the formula for the omega-3 Index?
Is a higher or lower number better? |
(EPA+DHA)/ Total Fatty Acids
You want a high % by eating more fish |
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What are some of omega-3 Drug interactions?
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- Blood Thinning medications (warfain, aspirin, clopidogrel)
- Blood Sugar Lowering medications: increases blood sugar levels Beneficial for: Cyclosporine, Cholesterol-lowering medications, NSAIDS NSAIDS with omega-3 decreases ulcers |
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What levels can be measured at non-fasting state?
Apo B/ Apo A-I should be less than what? Total C/ HDL should be less than what? |
Total Cholesterol
and HDL Apo B (LDL)/ Apo A-I (HDL) <0.9 Total C/ HDL <4.5 |
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What is the spontaneous cessation of blood loss from a damaged blood vessel
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Hemostasis
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Three main processes of Hemostasis
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1. Adhesion and activation of platelets
2. Fibrin formation (blood coagulation) 3. Vascular contraction of damaged blood vessels |
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What is the removal of a clot called?
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Fibrinolysis
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Explain the process that occurs after PGI2 binds to a platelet
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PGI2 binds to platelet
increase in cAMP Ca2+ sequation inhibiting platelet aggregation |
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due to exposure to collagen?
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ADP
5HT TXA causes aggregation |
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Name platelet signals that are activators
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ADP
Collagen Thrombin Thromboxanes Serotonin Epinephrine Antigen-Antibody Complex Viruses and Bacteria |
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Name platelet signals that are inhibitors
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Prostacyclin (PGI2)
cAMP Decreased levels of thrombin and thromboxanes |
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What does blood coagulation do?
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transforms soluble fibrinogen into insoluble fibers
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Enzyme that converts fibrinogen to fibrin
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Thrombin
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Thrombin activates what to further stabalize clots?
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Crosslinking action of Factor XIII
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Which is the dominant pathway in the body?
Intrinsic (tissue not in contact with blood) or Extrinsic (injured tissue contact with blood) |
Intrinsic
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What does the Intrinsic Pathway require besides IX and VII to make IXa and VIIa
also needed for production of Xa from A |
Ca2+
Phospholipid VIIIa |
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IIa is called what?
I is called what? II is called what? |
IIa- Thrombin
I- Fibrinogen II- Prothrombin |
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Coagulation proteins are inactivated by...
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alpha2- macroglobin
alpha2- antiplasmin Antithrombin III; Protein C |
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Proteins C and S inactivate which factors?
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Factor Va
Factor VIIIa |
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What is Fibrinolysis?
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conversion of inactive plasminogen to plasmin
Plasmin digests fibrin to limit the extent of thrombosis |
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clot that adheres to a vessel wall
clot that floats within the blood |
Thrombus
Embolus |
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White clot vs. Red clot
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White- found in rapidly flowing (arterial) blood; treated with antiplatelet drugs and anticoagulants
Red- found in slow moving (venous) or stagnant blood; treated with anticoagulants and fibrinolytic drugs |
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If clot forms in leg it is known as what?
If clot forms in lungs, it is known as what? If clot forms in the heart, it is known as what? |
Deep Vein Thrombosis
Pulmonary Embolism Heart Attack |
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Name some anticoagulants and what do these drugs affect?
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Argatobran
Lepirudin Warfarin taregets anticoagulant factors |
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Name antiplatelets and what they target
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Aspirin
Ticlopidine (irreversible) Clopidogrel (irreversible) Dipyridamole Abciximab Eptifibatide Tirofiban Targets platelets |
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Name some Thrombolytics and what do they target?
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Streptokinase
Anysoylated Targets plasminogen |
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Name some Antithrombotic agents and what do they target
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Aminocaproic acid
Tranexamic acid Aprotinin |
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What is Antithrombin III (ATIII)
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natural serine protease inhibitor that inhibits coagulation factors:
IXa Xa IIa (Thrombin) by binding to their active sites |
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How does Heparin Anticoagulate
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Heparin molecules bind ATIII inducing a conformation change that accelerates its rate of action about 1000-fold (inhibiting coagulation factors IXa, Xa, IIa)
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Difference between Regular Heparin and LMW Heparin
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Regular- blocks IXa, Xa, IIa, by binding to IIa and/or Xa
LMW- only inhibits Xa |
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What is the drug of choice for anticoagulation during Pregnancy?
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Heparin- cannot cross placenta
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What do you measure for monitoring parameters in patients taking Heparin?
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aPTT (Activated partial thromboplastin time)
should be 1.5-2x patients' baseline measures intrinsic pathway |
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Heparin is contraindicated in Patients that are what?
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bleeding
have hemophilia thrombocytopenia hypertension Do NOT take with Aspirin or positively charged drugs and aminoglycosides |
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Name 3 LMWH
LMW Heparins What is the target for these drugs? |
1. Enoxaparin (Lovenox)
2. Dalteparin (Fragmin) 3. Tinzaparin (Innnohep) Potent factor Xa inhibitor Given SC |
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How is the biological activity of LMW Heparins measured?
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Factor Xa inhibition assay
less monitoring than heparin No aPTT needed Monitor end stage renal disease |
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What drugs inhibits thrombin-factor IIa
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Lepirudin (Refludan)- Hirudin derivative from saliva of medicinal leeches; administered IV, aPTT monitorring recommended
Argatroban- side effect is bleeding |
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Name the Parenteral Anticoagulant that is purely synthetic derived and no variable biological activity
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Fondaparinux (ARIXTRA)
Selectively inhibits factor Xa by binding to ATIII well absorbed from SC route contraindicated with patients with severe renal impairment does not affect platelet function or actions No HIT (Heparin induced thromboyctopenia) |
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How is Warfarin administered and how does it work?
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Warfarin (Coumadin) is an oral anticoagulant
antagonist of vitamin K-cofactor in the hepatic synthesis of coagulation factors II, VII, IX, X and antocoagulant proteins C and S blocks reduction of oxidized vitamin K therefore blocking carboxylation targets synthesis of coagulation factors *Vitamin K epoxide Reductase* |
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Which anticoagulant has 100% bioavailability?
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Warfarin (Coumadin)
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Onset of action for Warfarin depends on the dissapearance of which factors?
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VII, IX, X, II
Peak effects may not be until 72-96 hours (3-5 days) which is the time required to deplete the pool of circulating clotting factors |
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Name some Indicatications for the use of Warfarin
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-prevent progression of acute deep vein thrombosis or pulmonary embolism
-prevention of venous thromboembolism during orthopedic or gynecological surgery - Prophylaxis in patients with acute MI, prosthetic heart valves, or chronic atrial fibrillation |
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What are Side Effects of Warfarin?
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Bleeding
skin lesions and skin necrosis purple toe syndrome |
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What drugs are included in Drug interactions with Warfarin
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Aspirin and phenylbutazone (inc. bleeding)
Antibiotics (decreases metabolsim of warfarin) Barbituates and Rifampin (decrease warfarin effectiveness by inducing microsomal P450 system) -Oral contraceptives (dec warfarin effect by inc. plasma clotting factors and decreasing ATIII) |
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What drugs decrease the anticoagulant effects of Warfarin
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Estrogen
Phenytoin Rifampin Barbiturates Vitamin K |
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What drugs increase the bleeding tendencies with Warfarin?
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Cephalosporins
Salicylates Adrenal corticosteroids NSAIDS |
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What drugs enhance anticoagulant effects of Warfarin?
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Oral antibiotics
Salicylates Alcohol Sulfonamides Cimetidine Amiodarone |
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How is Warfarin monitored?
What is the goal? |
Prothrombin time (PT)
International Normalized Ratio (INR) Goal: INR= 2-3 or INR= 2.5-3.5 (mechanical heart valves) |
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When should Warfarin be discontinued?
How is Warfarin toxicity treated? |
Discontinue if INR <5
administer large amount of Vitamin K (phytonatoide) if INR >5 serious bleeding with INR> 20 requires vitamin K, factor IX concentrates and fresh frozen plasma to replace clotting factors |
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Heparin vs Warfarin
Route Onset Duration Monitoring Antidoe for overdose |
Heparin vs Warfarin
Route IV or SC/ PO Onset Rapid/ Slow Duration Brief/ Prolonged Monitoring aPTT/ PT Antidoe for overdose Protamine/ Vitamin K |
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Oral anticoagulant that is a direct thrombine inhibitor
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Dabigatran (Pradaxa)
approved in Europe no monitoring |
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Inhibits synthesis of prostaglandins by decreasing endothelial synthesis of PGI2 and inhibitibiting the production of TXA2 by acetylating the active site of cyclooxygenase
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Aspirin
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Uses for Aspirin
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Prophylactic for transient cerebral ischemia
Reduce the incidence of recurrent MI Decrease mortality in post-myocardial infarction patients |
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Agents that irreversibly inhibit the binding of ADP to its receptor on platelets?
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1. Ticlopidine (prodrug)
2. Clopidogrel target is ADP |
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nucleotide that causes platelets to change shape and aggregate
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ADP
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Ticlopidine
Clopidogrel |
Ticlopidine- more severe side effects like nausea, vomiting, and diarrhea; NEUTROPENIA is most serious side effect; THROMBOCYTOPENIA also reported
Clopidogrel- prodrug converted via CYP450 enzyme; more favorable toxicity profile Both are prodrug |
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Black Box Warning for Clopidogrel
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CYP2C19 activation required by clopidogrel to convert it's active metabolite
higher cardiovascular events with patients with poor CYP2C19 metabolism |
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Direct acting oral ADP receptor inhibitor not requiring hepatic metabolism for activation
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Ticagrelor (Brilinta)
not approved in USA yet faster onset, more potent, short half-life, reversible greater incidence of dyspnea, ventricular pauses and increased levels of creatinine |
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vasodilator that inhibits platelet aggregation by increasing cellular concentration of cyclic AMP
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Dipyridamole (Persantine)
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Antiplatelet Agents that prevent binding of fibrinogen, vWF, and other adhesive molecules to GP IIb/IIIa receptor sites
Which one is derived from rattle snake venom which one is a fragment of humanized monoclonal antibody? |
Abciximab (Reopro)- antibody
Tirofiban (Aggrastat) Eptifibatide (Integrilin)- derived from rattle snake venom both inhibit GPIIb/IIIa receptor and are IV administered |
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How do Thrombolytic agents work?
Name two |
Anistreplase (Eminase)
Altepase activate plasminogen and dissolve both pathological thrombi and fibrin deposits at vascular sites venous thrombi are easier to lyse than arterial thrombi primarily used to dissolve clots in patients |
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nonspecific serine protease that digests fibrin and other plasma proteins including several coagulation factors
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Plasmin
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What is the endogenous inhibitor of plasmin
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alpha2-antiplasmin
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Thrombolytic Agent that is Anysoylated Plasminogen Activator Complex
what is the purpose of this? |
Anistreplase (Eminase)
protects streptokinase from hydrolysis when it is bound to plasminogen targets fibrinolytic clots |
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Thrombolytic Agent that is a tissue plasminogen activator (t-PA)
What is the purpose of this? |
Altepase
activates plasminogen bound to fibrin several hundred times more rapidly than unbound plasminogen used to lyse thrombi |
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Name the thrombolytic agents
recombinant forms of human tissue plasminogen activator (t-PA) a protein obtained from human urine protein obtainedfrom streptococci preformed complex of streptokinase and plasminogen-prodrug |
Alteplase (Activase)
Urokinase (Abbokinase) Streptokinase (Streptase) Anistreplase (Eminase) |
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Which thrombolytic agents directly convert plasminogen to plasmin
and which must combine with plasminogen first which must be released from plasminogen |
Urokinase and t-PA
Streptokinase Anistreplase and Streptokinase |
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Major side effect of Thrombolytic Agents
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Hemorrhage-intracranial bleeding
can be controlled by aminocaproic acid |
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Contraindications with Thrombolytic Agents
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Surgery within 10 days
Serious GI bleeding Hypertension history active bleeding |
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kinetic screening test that measures the recalcification time of plasma after incubation with phospholipid and kaolin using a semi-automated method (instrinsic system)
used to evaluate the adequacy of the extrinsic system |
APTT
Activated partial thromboplastin Time PT- Prothrombine Time measures the clotting ability for factors I, II, V, VIII, X |
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Repolarization is mainly determined by what?
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openings of the potassium channels, leading to potassium exit from the cells
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What is special about the pacemaker cells?
Which is the dominant pacemaker in the heart? |
spontaneous phase 4 depolarization
SA node is dominant over the AV node |
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Which class of drugs depresses the SA and AV potentials?
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CCB
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What is the Effective refractory period (ERP)?
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time elapsed from initiation of the action potential to the moment where a stimulus elicits a conducted response
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What determines the conduction velocity of the cell?
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phase 0 of the action potential (sodium entry)
steeper=faster conduction velocity |
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His-Purkinje/myocardial cells
vs Atrial cells |
His-Purkinje/myocardial cells- large sodium currents with large action potentials (no pacemaker activity)
Atrial Cells- shorter action potentials due to stronger repolarizing currents |
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Voltage-dependent potassium channels play a role in what phases?
K influx or K efflux? Potassium channels determine what about the action potential? |
Phases 2,3,4
K efflux duration |
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What does blocking the potassium currents do?
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causes slower repolarization
prolongs action potentials |
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Drugs that inhibit potassium currents
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Bretylium
Amiodarone Sotalol Quinidine Procainamide Dispyramide antibiotics and antidepressants |
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Voltage-dependent calcium channels are found in which phases? (efflux or influx)
what are the main type of calcium channels in the heart tissue? |
phase 2 (plateau)
Ca2+ influx L-type channels |
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L-type calcium channels are sensitive to which drugs?
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DHP CCB and non DHP CCB
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What protein does Calcium bind to once it goes back into the sarcoplasmic reticulum?
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Calsequestrin
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through what methods does the Ca leave the cell?
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sodium-calcium exchange
(2 Ca ou and 3 Na in0 Ca-ATPase pummp taken up by sarcoplasmic reticulum |
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By decreasing calcium entry, CCBs are expected to decrease what?
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decrease contractility
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In SA and AV nodes, depolarization is mainly due to what?
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calcium inward currents (little sodium influx0
CCB depress SA and AV potentials reducing Hr and conduction velocity through the AV node |
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Sodium-Potassium ATPase exchanges what and where?
Drug that inhibits it |
3 Na out; 2 K in
Digoxin augments strength of contraction because high level of Na will trigger the Na/Ca exchanger to let Na out and bring Ca in |
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What happens during each phase?
P wave: P-R interval: QRS complex: ST segment: T wave: QT interval: |
What happens during each phase?
P wave: atrial depolarization P-R interval: atrial repolarization? QRS complex:ventricular depolarization ST segment: beginning of repolarization T wave: Ventricular Repolarization QT interval: |
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Range for normal resting HR
Pacemaker site? |
60-100 b/min
SA node |
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___________ reflects the capability of a cardiac cell to depolarize spontaneously during phase 4 to reach threshold potential and to depolarize completely without being externally stimulated
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Automaticity
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Capability of a resting, polarized cardiac cell to depolarize in response to an electrical stimulus. All cardiac cells have this capability
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Excitability
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Mechaisms by which arrhythmias are produced?
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1. Increased automaticity
2. Afterdepolarizations 3. Reentry |
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Increased automacticity can be caused by what?
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SNS activation
Beta stimulation Low potassium Fiber stretch Inhibition parasympathetic acitivity anticholinergic drugs OR increased automacticity in non-pacemaker cells due to ischemia of ventrcular cells or anti-arrhythmic drugs |
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Drugs that prolong the QT interval
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Antimicrobials:
macrolides (erythromycin, chlarithromycin) Pentamidine Fluoroquinolones (grepafloxacin, moxifloxacin, levofloxacin) Tricyclic antidepressants: imipramine desipramine amitrypiline doxepin Thioridazine, mesoridazine, haloperidol, resperidone, ziprasidone, quetiapine Cisapride Indapamide |
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How do drugs like azole antifungul agents prolong the QT interval?
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block the metabolsim of terfenadine
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What is the difference between EAD and DAD?
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Early afterdepolarization (EAD) occurs during phase 3- determined by calcium currents
Delayed afterdepolarization (DAD) arise after action potential has completed- sodium and calcium currents determine the upstroke of DAD |
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AV nodal block can be achieved by what?
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increased vagal tone
adenosine verapamil diltiazem beta adrenergic blockers digitalis |
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What are the classifications for anti-arrhythmic drugs?
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Type 1: Sodium Channel Blockers
Type 2: Beta Blockers Type 3: Potassium channel blockers Type 4: Calcium Channel Blockers |
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Names for type 1 anti-arrhythmic sodium channel blockers
IA IB IC |
Names for type 1 anti-arrhythmic sodium channel blockers
IA- Quinidine, Procainamide, Disopyramide (prolong action potential) IB- Lidocaine, Phenytoin, Tocainide, Mexiletine (shorten action potential) IC- Flecainide, propafenone (slow conduction velocity Moricizine- type 1 drug with all three characteristics |
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Names of Type II Anti-Arrhythmic Beta Blockers
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depresses phase 4
propranolol sotalol (also type III) acetobutolol esmolol metoprolol nadolol atenolol |
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What is the difference between EAD and DAD?
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Early afterdepolarization (EAD):occurs during phase 3 and is determined by calcium currents
Delayed afterdepolarization (DAD): arise when the action potential has completed and is determined by sodium and calcium channels |
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What are the classifications for anti-arrhythmic drugs?
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type 1- sodium channel blockers
type 2- beta blockers type 3- Potassium channel blockers type 4- calcium channel blockers |
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Type I Anti-arrhythmics: Sodium-channel blockers
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Type IA: Quinidine, procainamide, disopyramide (depress phase 0 and prolong action
potential) . Type IB: Lidocaine, phenytoin, tocainide, mexiletine (depress phase 0 slightly, may shorten action potential). Type IC: Flecainide, propafenone (marked depression of phase 0, slow conduction velocity). Note: moricizine is a type I drug, that shares characteristics of IA, IB and IC. |
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Type II Anti-arrhythmics. Beta Blockers
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Propranolol, sotalol, acetobutolol, esmolol, metoprolol, nadolol, atenolol.
Sotalol may have type III effects. |
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Type III Anti-arrhythmics. Potassium channel blockers
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(prolong phase 3 and the action
potential). Bretylium, amiodarone, sotalol. Amiodarone has also type I, II and IV actions. |
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Type IV Anti-arrhythmics. Calcium channel Blockers.
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Verapamil, diltiazem, bepridil.
Bepridil has additional type III effects. |
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effects induced by sodium channel blockers
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1. Decreased excitability and automaticity
2. Decreased conduction velocity in Purkinje, myocardial and atrial cells 3. Increase refractoriness: more repolarization |
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What are the sodium channel blockers with addition effects?
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quinidine,
procainamide and disopyramide block K-channels involved in repolarization, prolonging action potential duration and cell refractoriness (QRS and QT prolongation. Type IA |
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It is a sodium and potassium channel blocker. It reduces excitability and automaticity, and
prolongs refractoriness. · Prolongs QT interval (potassium channel blocking effect), and produces a modest increase in QRS duration (sodium channel blockade of intermediate recovery time constant). · Because of the QT prolongation it may increase the incidence of after-depolarizations mainly at low heart rates, particularly if hypokalemia is present. |
Quinidine
Type IA |
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Clinical use for Quinidine (Type IA)
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maintenance of sinus rhythm in patients with atrial fibrillation
conversion of atrial fibrillation |
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Non-Cardiac side effects of Quinidine (Type IA)
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Diarrhea (30-50% patients).
· Cinchonism: headache, dizziness tinnitus (improves with dose reduction). · Immunological reactions: hepatitis, thrombocytopenia, Lupus-like syndrome, myasthenia gravis |
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Why shouldn’t quinidine or disopyramide used alone to convert atrial flutter or atrial fibrillation
to normal sinus rhythm ? |
Quinidine slows conduction velocity in the atrium, but the ventricular rate may increase due to its anicholinergic effects
An AV nodal blocker like Digoxin should be a pretreatment |
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Similar electrophysiological effects and clinical uses than quinidine.
· No alpha blocking activity. · Strong anticholinergic activity (dry mouth, constipation, urinary retention, precipitation of glaucoma). Its metabolite (mono-N-dealkyl-disopyramide) has stronger anticholinergic activity than the parent drug. · Eliminated by metabolism and urinary excretion. |
Disopyramide
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Similar electrophysiological effects and clinical uses than those of quinidine and
disopyramide. · It does not have alpha blocking or anticholinergic activity. · It is rapidly eliminated (half life: 3-4 hours), requiring repeated dosing and sustained release formulations. Its metabolite: N-acetyl procainamide (NAPA) blocks K channels, but has no effect on sodium channels. Parent drug prolongs QRS and QT, metabolite prolongs QT. NAPA is eliminated by the kidney (half life 6-10 hours). Can induce Torsades de pointes. |
Procainamide
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Side effects of Procainamide?
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leads to positive antinuclear antibodies (ANA) due to druginduced
lupus syndrome Decreased neutrophilsÿÿÿ >o |
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Common features for quinidine, disopyramide and procainamide
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Very similar mechanism of action and clinical indications.
· Effects increased by hypokalemia: correct serum potassium levels prior to initiating drug treatment. · Caution in patients with depressed contractility and in patients receiving treatment with cardiodepressant drugs, such as beta-blockers, CCB and other type IA drugs. It may induce CHF. High incidence of immunological side effects. · Frequent monitoring of WBC, differential, platelets, ANA and LFTs. · Excessive widening of QRS and QT prolongation (> 50%) are indicators of cardiotoxicity (lower the dose) (must closely monitor ECG). · Can induce Torsade de Pointes (due to QT prolongation). · Must cardiovert or digitalize before initiating Tx for atrial fibrillation or flutter. |
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Differences among quinidine, disopyramide and procainamide
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Quinidine- cinchonism, diarrhea, stronger anitcholinergic effects, greater alpha blocking activity
Procainamide- NAPA active antiarrhythmic metabolite, higher incidence of drug-induced lupus, shorter half-life and lower protein binding |
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Affects caused by Lidocain (type IB anti-arrhythmic)
side effects? |
Lidocaine: is an amide local anesthetic.
· Blocks open and inactivated sodium channels (greater preference for inactivated channels). · Main use: acute IV treatment of VT or VF. · Decreases incidence of VF in patients with acute MI. · Indicated for acute management of ventricular arryhthmias occurring during cardiac manipulations, such as cardiac surgery or in relation to an acute MI. · Not useful in atrial arryhthmias. · Lidocaine is not given PO, because of its first pass metabolism, and the need of rapid action in VT and VF. · Side effects: seizures and other CNS side effects are observed when a large IV dose is given rapidly. Proarrhythmic action. Malignant hypertermia can be produced. |
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Mexiletine and Tocainide (type IB)
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· These agents are analogs of lidocaine with less first-pass metabolism. Their
electrophysiological actions are similar to those of lidocaine.n |
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Phenytoin (type 1B)
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Phenytoin.
· Anticonvulsant drug (grand mal and psychomotor seizures; control of status epilepticus of the grand mal type.). · Like lidocaine binds to inactivated sodium channels and has a rapid recovery from block. · Undergoes extensive first-pass metabolism and its metabolism is saturable. Small increases in dose may produce large increases in plasma levels and toxicity (same as propafenone). It is highly protein bound. Correct plasma levels based on albumin concentrations. 10 · Toxicity: CNS side-efects: ataxia (incoordination), nistagmus, mental confusion, slurred speech. Gingival hyperplasia. Rash and fever. Hematologic: bone marrow depression, low WBC counts, low platelets, macrocytosis and megaloblastic anemia (sensitive to folic acid).cat |
